Lead (Pb) continues to pose health risks for those sectors of the population in which exposure is highest, particularly individuals of lower socioeconomic status and workers in the construction trades. In addition to notorious effects on cognitive function, chronic Pb exposure is associated with hypertension and cardiovascular disease. Experimental studies from our laboratory reveal that chronic Pb exposure permanently alters corticosterone levels and stress reactivity in rats. If similar alterations in the hypothalamic pituitary adrenal axis (HPA) are demonstrated among humans chronically exposed to Pb, then such alterations may contribute over time to disease vulnerability. Aim 1 of this translational study is to assess HPA axis, sympathoadrenergic (SAS), and blood pressure reactivity to an acute stressor among healthy workers whose chronic exposure to Pb is documented by Cd K x-ray fluorescence (K-XRF). Aim 2 is to evaluate the effect of genetic polymorphisms associated with glucocorticoid receptors and Pb metabolism on glucocorticoid response to stress. Fifty-five healthy Pb-exposed subjects and 55 healthy unexposed controls, ages 30 to 50, will be recruited from the construction trades. Tibial K-XRF will be used to estimate chronic exposure to Pb. Subjects will perform the Trier Stress, comprised of a public speaking and math task. ACTH, cortisol, epinephrine, norepinephrine, and blood pressure will be assessed before, during and following the stressor. Heart rate reactivity will be used to assess the effect of individual stress reactivity on glucocorticoid and catecholamine response to stress. In coordination with an existing R01, basic science animal studies are planned to incorporate catecholamine and blood pressure stress responsivity among animals exposed to Pb in regimens similar to those observed in human populations and to elucidate mechanisms underlying the relationship between Pb exposure, HPA axis alterations, and blood pressure. [unreadable] [unreadable] [unreadable] [unreadable]